Genotype Combinations Research Articles

MTOR gene variant rs2295080 might be a risk factor for atherosclerosis in Iranian women with type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus, one of the most prevalent metabolic disorders worldwide, is closely linked with an enhanced risk of atherosclerosis. However, the molecular mechanism of this linkage is not still clear. Genetic variations in the mTOR gene may increase the susceptibility of individuals to these diseases.MethodsOne hundred nine diabetic patients and 375 healthy subjects participated in this study. mTOR Single Nucleotide Polymorphism (SNP) rs2295080 was determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsComparison of genotypic, allelic, and genotypic combination frequencies between cases and controls revealed no significant result. Nevertheless, the frequency of rs2295080 GT + TT genotype was significantly more in diabetic women with atherosclerosis compared with those without atherosclerosis (p = 0.047). Besides, the rs2295080 G allele was more frequently detected in diabetic women without atherosclerosis compared to those with atherosclerosis (p = 0.046).ConclusionThe rs2295080 GT + TT genotype predisposes Iranian diabetic women to atherosclerosis, while the rs2295080 G allele protects them against atherosclerosis. However, additional experiments using larger sample sizes are needed to verify this result.

HPV infection patterns and viral load distribution: implication on cervical cancer prevention in Western Kenya.

Human papillomavirus (HPV) coinfection remains common globally. However, its clinical significance compared to mono-infection remains controversial. Further, the epidemiology of HPV genotype combination in coinfection is not well studied in Kenya. . Between June and August 2023, a cross-sectional facility-based survey enrolled 434 women aged 16-68 years using purposive sampling strategy. Structured questionnaire was obtained from each woman regarding demographic and sexual behavior characteristics. Cervical specimen was collected from each participant and analyzed using RIATOL assay to determine HPV genotypes and viral load. Overall, HPV 52 was the most frequently detected HPV strain. The mean HPV viral load was elevated among coinfected women than those with mono-infection but there was no evidence to support differences in viral load in the two groups (P = 0.113). Mono-infection was common (58.52%). HPV 16 was noted to have a near equal presence both in mono-infection and coinfection (52.17% and 47. 83%), respectively. HPV 33 (alpha 9) and 45 (alpha 7) had the greatest preference for each other compared to all other HPV interactions. HPV 52 is the most prevalent HPV in the population supporting the need for the nonavalent HPV vaccine. Mono-infection with HPV 16 remains common corroborating the relevance of bivalent vaccine in resource limited setting where nonavalent vaccines may be unavailable. The frequent coinfection preference of HPV 33 and 45 (alpha 9 and alpha 7, respectively) pauses the need for further concurrent characterization. HPV vaccination and education on safe sexual behaviors is key in reducing HPV coinfection.

Association of Polymorphisms in FSHR, ESR1, and BMP15 with Primary Ovarian Insufficiency and Meta-Analysis.

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088-29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134-31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059-3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women.

Distribution of CYP3A4 and CYP3A5 Polymorphisms and Genotype Combination Implicated in Tacrolimus Metabolism.

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5 and CYP3A4 is caused by Single Nucleotide Polymorphisms (SNPs) of genes encoding these proteins. The present study investigated the genetic polymorphisms CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in the Tunisian population. We included in this study, Tunisian healthy subjects and renal transplant recipients receiving tacrolimus. CYP3A4 and CYP3A5 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to the genotypic combination of the three CYP polymorphisms, we have identified for the first time four metabolizers statuses: slow metabolizers (SM), intermediate metabolizers (IM), high metabolizers (HM), and extensive metabolizers (EM). A total of 101 renal transplant patients and 102 healthy subjects were included. Our results showed that the predominant alleles in the Tunisian population are a wild type of CYP3A4*1B (0.87), likewise CYP3A4*22 (0.975) and CYP3A5*3 (0.82). The genotype frequencies of CYP3A4*1B, CYP3A4*22, and CYP3A5*3 were found to be 3.9%, 0.0%, and 69.5%, respectively. Also, we found a significant linkage disequilibrium between CYP3A4*1B and CYP3A5*3. We approved that the IM is the predominant phenotype in our population with 124 patients followed by and EM with 41 patients, HM in 29 patients and SM in 9 patients. These results showed that Tunisians are most similar to Caucasians. The genetic background of these enzymes CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in this study are important in the prescription of personalized medicine.

A Heuristic Approach to Analysis of the Genetic Susceptibility Profile in Patients Affected by Airway Allergies.

Allergic respiratory diseases such as asthma might be considered multifactorial diseases, having a complex pathogenesis that involves environmental factors and the activation of a large set of immune response pathways and mechanisms. In addition, variations in genetic background seem to play a central role. The method developed for the analysis of the complexities, as association rule mining, nowadays may be applied to different research areas including genetic and biological complexities such as atopic airway diseases to identify complex genetic or biological markers and enlighten new diagnostic and therapeutic targets. A total of 308 allergic patients and 205 controls were typed for 13 single nucleotide polymorphisms (SNPs) of cytokine and receptors genes involved in type 1 and type 2 inflammatory response (IL-4 rs2243250 C/T, IL-4R rs1801275A/G, IL-6 rs1800795 G/C, IL-10 rs1800872 A/C and rs1800896 A/G, IL-10RB rs2834167A/G, IL-13 rs1800925 C/T, IL-18 rs187238G/C, IFNγ rs 24030561A/T and IFNγR2 rs2834213G/A), the rs2228137C/T of CD23 receptor gene and rs577912C/T and rs564481C/T of Klotho genes, using KASPar SNP genotyping method. Clinical and laboratory data of patients were analyzed by formal statistic tools and by a data-mining technique-market basket analysis-selecting a minimum threshold of 90% of rule confidence. Formal statistical analyses show that IL-6 rs1800795GG, IL-10RB rs2834167G positive genotypes, IL-13 rs1800925CC, CD23 rs2228137TT Klotho rs564481TT, might be risk factors for allergy. Applying the association rule methodology, we identify 10 genotype combination patterns associated with susceptibility to allergies. Together these data necessitate being confirmed in further studies, indicating that the heuristic approach might be a straightforward and useful tool to find predictive and diagnostic molecular patterns that might be also considered potential therapeutic targets in allergy.

Grafting in Coffea canephora: a strategy to enhance growth and photosynthetic rates for environments with contrasting water availabilities

Water deficit is one of the main limiting factors for the yield in most regions where Coffea canephora is cultivated. This problem has been amplified by the climate changes in recent years. The objective of this work was to study the response of grafting combinations between genotypes of C. canephora, cultivated in contrasting conditions of water availability, and their effects over the initial growth and photosynthetic rates of the plants. For this end, grafted plants with four combinations of genotypes (201/14, 201/RT, 02/14 and 02/RT) were submitted to two contrasting conditions of water supply (80% and 25% of available water in the soil). The initial growth, dry matter accumulation, and leaf gas exchanges were evaluated. Under abundant water supply, the grafting combination 02/RT achieved higher initial growth, whereas 02/14 maintained higher growth under conditions of water deficit. Under adequate water supply, the combinations 201/14 and 201/RT stand out regarding water use parameters, while in conditions of water deficit, the combination 201/14 was capable of keeping higher efficiencies.

Evaluating the evidence for genotype-informed Bayesian dosing of tacrolimus in children undergoing solid organ transplantation: A systematic literature review.

Tacrolimus, a calcineurin inhibitor, is a highly effective immunosuppressant used in solid organ transplantation (SOT). However, it is characterized by a narrow therapeutic range and high inter-patient variability in pharmacokinetics. Standard weight-based dosing followed by empiric dose titration is suboptimal in controlling drug concentrations, increasing risk of rejection or toxicity, particularly in the initial months post transplantation. This review explores the potential of combined pre-transplant genotyping and pharmacokinetic (PK) modelling to improve tacrolimus dosing in paediatric SOT recipients. A systematic search of Medline, Embase and Cochrane databases identified studies published between March 2013 and March 2023 that investigated genotype- and PK model-informed tacrolimus dosing in children post-SOT. The Newcastle-Ottawa Scale assessed study quality. Seven studies encompassing paediatric kidney, heart, liver and lung transplants reported using genotype and model-informed dosing. A combination of clinical and genetic factors significantly impacts tacrolimus clearance and thus initial dose recommendation. Body size, transplant organ and co-medications were consistently important, while either time post-transplant or haematocrit emerged in some studies. Several models were identified, however, with limitations evident in some and with absence of evidence for their effectiveness in optimizing initial and subsequent dosing. This review highlights the development of PK models in paediatric SOT that integrate genotype and clinical covariates to personalize early tacrolimus dosing. While promising, prospective studies are needed to validate and confirm their effectiveness in improving time to therapeutic concentrations and reducing under- or overexposure. This approach has the potential to optimize tacrolimus therapy in paediatric SOT, thereby improving outcomes.

Impact of genotypic mixture on soybean (Glycine max) pest population

An experiment was conducted during rainy (kharif) seasons of 2018 and 2019 at the ICAR-Indian Institute of Soybean Research, Indore, and Madhya Pradesh to study the impact of genotypic mixture on soybean [Glycine max (L.) Merr.] pest population. A total of 16 soybean genotypes and 4 genotypic mixtures were evaluated for relative efficacy in management of insect-pests of soybean. Among the 20 treatments, the plots with genotypic mixtures had lowest population of Spodoptera exigua Hubner and at par with each other. In case of Spodoptera litura Fabricius, tussock moth, blue beetle and grey weevil management, a mixture of the genotypes JS-9560, JS-20-34, MAUS-47 and MACS-1460 was found most effective treatment. The plots with the genotypic mixtures of NRC-37, JS-9752, RSC-1046 and RKS-113 supported the least population of semiloopers. However, lowest population of leaf miner and girdle beetle was recorded in plots of JS-20-34 while the least population of stem fly was recorded in RSC-1046. The differences observed due to the genotypic combinations may be used for developing inset-pest management programmes in soybean.

Rotavirus A Infection Prevalence and Spatio-Temporal Genotype Shift among Under-Five Children in Amhara National Regional State, Ethiopia: A Multi-Center Cross-Sectional Study.

Background: Globally, rotavirus (RV) A (RVA) is the most common cause of severe and sometimes fatal diarrhea in young children. It is also the major cause of acute gastroenteritis among children in Ethiopia. Currently, the WHO has prequalified four RVA vaccines for universal childhood immunization. Ethiopia introduced the monovalent Rotarix vaccine into its national immunization program in 2013. Since then, only a few studies on the burden and genotype distribution of RVA infection post-vaccine introduction have been conducted (mostly at sentinel surveillance sites). Therefore, this study aimed to assess RVA prevalence and genotype distribution among children under five years in Ethiopia (February 2021-December 2022). Methods: This multi-center hospital-based cross-sectional study involved 537 diarrheic children under-five years old. Rotavirus A detection was conducted using a one-step reverse-transcriptase polymerase chain reaction (RT-PCR). Genotyping was conducted by Sanger sequencing of the VP7 (complete) and VP4 (partial) genes. Descriptive analysis and Pearson's chi-squared test were carried out using SPSS version 29. Phylogenetic analysis with 1000 bootstrap replicates was performed using MEGA version 11 software. Statistical significance was set at p < 0.05 for all analyses. Results: The prevalence of RVA infection among diarrheic children was 17.5%. The most prevalent G-types identified were G3 (37%), the previously uncommon G12 (28%), and G1 (20%). The predominant P-types were P[8] (51%), P[6] (29%), and P[4] (14%). The three major G/P combinations observed were G3P[8] (32.8%), G12P[6] (28.4%), and G1P[8] (19.4%). Phylogenetic analysis revealed clustering of Ethiopian strains with the globally reported strains. Many strains exhibited amino acid differences in the VP4 (VP8* domain) and VP7 proteins compared to vaccine strains, potentially affecting virus neutralization. Conclusions: Despite the high RVA vaccination rate, the prevalence of RVA infection remains significant among diarrheic children in Ethiopia. There is an observable shift in circulating RVA genotypes from G1 to G3, alongside the emergence of unusual G/P genotype combinations such as G9P[4]. Many of these circulating RVA strains have shown amino acid substitutions that may allow for neutralization escape. Therefore, further studies are warranted to comprehend the emergence of these unusual RVA strains and the diverse factors influencing the vaccine's diminished effectiveness in developing countries.

Association of Genetic Profile with Muscle Mass Gain and Muscle Injury Prevention in Professional Football Players after Creatine Supplementation.

In recent years, the study of creatine supplementation in professional athletes has been of great interest. However, the genetics involved in response to supplementation is unknown. The aim of this study was to analyse, for the first time, the relationship between muscle performance-related genes and the risk of an increased body mass index (BMI) and muscle mass and a decrease in fat mass in professional football players after creatine supplementation. For this longitudinal study, one hundred and sixty-one men's professional football players were recruited. The polymorphisms ACE I/D, ACTN3 c.1729C>T, AMPD1 c.34C>T, CKM c.*800A>G, and MLCK (c.49C>T and c.37885C>A) were genotyped using Single-Nucleotide Primer Extension (SNPE). To assess the combined impact of these six polymorphisms, a total genotype score (TGS) was calculated. The creatine supplementation protocol consisted of 20 g/day of creatine monohydrate for 5 days (loading dose) and 3-5 g/day for 7 weeks (maintenance dose). Anthropometric characteristics (body mass index (BMI), fat, and muscle mass) were recorded before and after the creatine supplementation protocol. Characteristics of non-contact muscle injuries during the 2022/2023 season were classified according to a consensus statement for injury recording. The results showed that the allelic frequencies of ACE and AMPD1 differed between responders and non-responders in muscle mass increase (all p < 0.05). Players with a TGS exceeding 54.16 a.u. had an odds ratio (OR) of 2.985 (95%CI: 1.560-5.711; p = 0.001) for muscle mass increase. By contrast, those with a TGS below 54.16 a.u. had an OR of 9.385 (95%CI: 4.535-19.425; p < 0.001) for suffering non-contact muscle injuries during the season. The increase in BMI and muscle mass in response to creatine supplementation in professional football players was influenced by a TGS derived from the combination of favourable genotypes linked to muscle performance. The CC genotype and C allele of AMPD1 were particularly associated with a higher likelihood of muscle mass increase under creatine supplementation in this group of professional football players.

Genetic Variants in p53 Pathway Genes Affect Survival of Patients with HBV-Related Hepatocellular Carcinoma.

P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC. We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal. We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10-1.48) and 0.77 (0.66-0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (P trend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells. We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.

Lettuce Genotype-Dependent Effects of Temperature on Escherichia coli O157:H7 Persistence and Plant Head Growth

Lettuce has been commonly associated with the contamination of human pathogens, such as Escherichia coli O157:H7 (hereafter O157:H7), which has resulted in serious foodborne illnesses. Contamination events may happen throughout the farm-to-fork chain, when O157:H7 colonizes edible tissues and closely interacts with the plant. Environmental conditions have a significant impact on many plant–microbe interactions; however, it is currently unknown whether temperature affects O157:H7 colonization of the lettuce phyllosphere. In this study, we investigated the relationship between elevated growth temperatures, O157:H7 persistence, and lettuce head growth using 25 lettuce genotypes. Plants were grown under optimal or elevated temperatures for 3.5 weeks before being inoculated with O157:H7. The bacterial population size in the phyllosphere and lettuce head area was estimated at 0- and 10-days postinoculation (DPI) to assess bacterial persistence and head growth during contamination. We found that growing temperature can have a positive, negative, or no effect on O157:H7 persistence depending on the lettuce genotype. Furthermore, temperature had a greater effect on head area size than the presence of O157:H7. The results suggested that the combination of plant genotype and temperature level is an important factor for O157:H7 colonization of lettuce and the possibility to combine desirable food safety traits with heat tolerance into the lettuce germplasm.

ACKR1 gene polymorphisms in Bombay blood group (Oh) individuals of Indian origin

BackgroundACKR1 blood group genes exhibit a high degree of polymorphisms with varying allele distribution seen among different populations and ethnic groups. The study aimed to genotype ACKR1 antigens and to establish FY allele frequency among the individuals with the Bombay (Oh) blood group phenotype. Materials and methodsACKR1 phenotype and genotype frequencies were estimated on 160 individuals typed as Oh and were compared with 100 non-oh blood donors from Mumbai, India by molecularly genotyping via PCR-RFLP. ResultsThe allelic and genotypic frequency of T(−67)C polymorphism showed the dominance of T allele and TT genotype [OR= 3.26 (0.59–17.99)] in both the study groups. The ACKR1 null (Fya-b-) phenotype was not found in the tested group. While the genotypic combination among the Oh group individuals was FYA/FYB (45.3 %), FYA/FYA (42.7 %), and FYB/FYB (12 %), in the non-Oh group donors, it was observed as FYA/FYB (53.3 %), FYA/FYA (39.1 %), and FYB/FYB (7.6 %).The haplotype TGGGC occurred in 38.4 % of the Oh group, but in non-Oh donors, it was found to be 50.9 % [OR = 1.820 (1.196–2.771)], and the difference was statistically significant (p = 0.005). Similarly, the TGGGT haplotype was found at a frequency of 12.7 % in non-Oh donors and 27.1 % in Oh group [OR= 0.411 (0.234–0.722)] (p = 0.001). ConclusionsThis study shows the prevalence of ACKR1 gene polymorphisms, including weak ACKR1 antigens in Oh individuals with a high frequency of haplotype TGGGC. The present study demonstrated for the first time the genotypes FyBweak, FyAweak and Fy Aweak/FyBESon RBC membranes in Indian subjects with Oh phenotype.

Investigating the role of RNA-binding protein Ssd1 in aneuploidy tolerance through network analysis.

RNA-binding proteins (RBPs) play critical cellular roles by mediating various stages of RNA life cycles. Ssd1, an RBP with pleiotropic effects, has been implicated in aneuploidy tolerance in Saccharomyces cerevisiae but its mechanistic role remains unclear. Here we used a network-based approach to inform on Ssd1's role in aneuploidy tolerance, by identifying and experimentally perturbing a network of RBPs that share mRNA targets with Ssd1. We identified RBPs whose bound mRNA targets significantly overlap with Ssd1 targets. For 14 identified RBPs, we then used a genetic approach to generate all combinations of genotypes for euploid and aneuploid yeast with an extra copy of chromosome XII, with and without SSD1 and/or the RBP of interest. Deletion of 10 RBPs either exacerbated or alleviated the sensitivity of wild-type and/or ssd1 Δ cells to chromosome XII duplication, in several cases indicating genetic interactions with SSD1 in the context of aneuploidy. We integrated these findings with results from a global over-expression screen that identified genes whose duplication complements ssd1 Δ aneuploid sensitivity. The resulting network points to a sub-group of proteins with shared roles in translational repression and p-body formation, implicating these functions in aneuploidy tolerance. Our results reveal a role for new RBPs in aneuploidy tolerance and support a model in which Ssd1 mitigates translation-related stresses in aneuploid cells.

Molecular assessment of voltage-gated sodium channel (VGSC) gene mutations in Rhipicephalus microplus from Guangxi, China

BackgroundPyrethroid chemicals are one of the main acaricides used against ticks. Resistance to these chemicals has been reported to be associated with mutations in the voltage-gated sodium channel (VGSC) gene of the Rhipicephalus microplus. This study investigates R. microplus resistance to pyrethroids in Guangxi region of China, marking one of the first research efforts in this area. The findings are intended to provide vital baseline for the effective implementation of localized tick control strategies.MethodsFrom March to July 2021, 447 R. microplus tick samples were collected from five prefecture-level cities in Guangxi. Allele-specific polymerase chain reaction (AS-PCR) was used to amplify segments C190A and G215T of the domain II S4-5 linker and T2134A of domain III S6 in the VGSC, to detect nucleotide mutations associated with resistance to pyrethroid acaricides. Subsequent analyses were conducted to ascertain the prevalence, types of mutations, and genotypic distributions within the sampled populations.ResultsMutations within VGSC gene were identified across all five studied populations of R. microplus, although the mutation rates remained generally low. Specifically, the most prevalent mutation was C190A, observed in 4.9% of the samples (22/447), followed by G215T at 4.0% (18/447), and T2134A at 1.3% (6/447). The distribution of mutations across three critical sites of the VGSC gene revealed four distinct mutation types: C190A, G215T, C190A + G215T, and T2134A. Notably, the single mutation C190A had the highest mutation frequency, accounting for 4.3%, and the C190A + G215T combination had the lowest, at only 0.7%. The analysis further identified seven genotypic combinations, with the wild-type combination C/C + G/G + T/T predominating at a frequency of 90.4%. Subsequently, the C/A + G/G + T/T combination was observed at a frequency of 4.3%, whereas the C/C + T/T + T/T combination exhibited the lowest frequency (0.2%). Additionally, no instances of simultaneous mutations at all three sites were detected. Geographical differences in mutation types were apparent. Both samples from Hechi to Chongzuo cities exhibited the same three mutation types; however, C190A was the most prevalent in Hechi, while G215T dominated in Chongzuo. In contrast, samples from Beihai to Guilin each exhibited only one mutation type: G215T occurred in 12.5% (4/32) of Beihai samples, and C190A in 7.5% (4/53) of Guilin samples.ConclusionsThese findings underscore the relatively low frequency of VGSC gene mutations in R. microplus associated with pyrethroid resistance in the Guangxi, China. Moreover, the variation in mutation types and genotypic distributions across different locales highlights the need for regionalized strategies in monitoring and managing pyrethroid resistance in tick populations. This molecular surveillance is crucial for informing targeted control measures and mitigating the risk of widespread resistance emergence.Graphical

Helicobacter pylori Cytotoxin-Associated Gene A (cagA) and Vacuolating Cytotoxin Gene A (vacA) Genotypes in Gastrointestinal Patients From Central Thailand.

Introduction The development of diseases associated with Helicobacter pylori(H. pylori) infection is closely linked to its virulence genes, which vary by geographic region. This study aimed to determine the prevalence of H. pylori cytotoxin-associated gene A (cagA) and vacuolating cytotoxin gene A (vacA) genes and their genotypes in patients with gastrointestinal diseases. Methods Patients diagnosed with gastrointestinal disease based on endoscopic findings were recruited for the study. Gastric biopsies were collected to screen for H. pylori infection using polymerase chain reaction (PCR). Subsequently, infected samples were tested forcagAand vacA genes, and their genotypes were analyzed by sequencing. Results Among 250 cases, 56% (140/250) exhibited gastrointestinal diseases. Of these cases, 32.1% (45/140) were infected with H. pylori. Regarding gene detection, 40 (88.9%)samples were positive for cagA, while all samples were positive for vacA. For cagA, the Western type with the ABC pattern was the most prominent. There was a statistically significant association between cagA genotypes and clinical outcomes, with the Western type being more prevalent in gastritis patients. For vacA, there was a high prevalence of the s1 and i1, while the m1 and m2 showed similar prevalence. In our combined analysis, the dominant vacA genotype combinations were s1m1i1 (46.7%). There were no statistical differences between the vacA genotypesand clinical outcomes (P > 0.05). Conclusion This study revealed a high prevalence of H. pylori cagA and vacA genes, but there were variations in their genotypes. A correlation was observed between the Western-type cagA and gastritis; however, no association was found between vacA genotypes and clinical outcomes.

Comparative Uptake Patterns of Radioactive Iodine and [18F]-Fluorodeoxyglucose (FDG) in Metastatic Differentiated Thyroid Cancers.

Background: Metastatic differentiated thyroid cancer (DTC) represents a molecularly heterogeneous group of cancers with varying radioactive iodine (RAI) and [18F]-fluorodeoxyglucose (FDG) uptake patterns potentially correlated with the degree of de-differentiation through the so-called "flip-flop" phenomenon. However, it is unknown if RAI and FDG uptake patterns correlate with molecular status or metastatic site. Materials and Methods: A retrospective analysis of metastatic DTC patients (n = 46) with radioactive 131-iodine whole body scan (WBS) and FDG-PET imaging between 2008 and 2022 was performed. The inclusion criteria included accessible FDG-PET and WBS studies within 1 year of each other. Studies were interpreted by two blinded radiologists for iodine or FDG uptake in extrathyroidal sites including lungs, lymph nodes, and bone. Cases were stratified by BRAF V600E mutation status, histology, and a combination of tumor genotype and histology. The data were analyzed by McNemar's Chi-square test. Results: Lung metastasis FDG uptake was significantly more common than iodine uptake (WBS: 52%, FDG: 84%, p = 0.04), but no significant differences were found for lymph or bone metastases. Lung metastasis FDG uptake was significantly more prevalent in the papillary pattern sub-cohort (WBS: 37%, FDG: 89%, p = 0.02) than the follicular pattern sub-cohort (WBS: 75%, FDG: 75%, p = 1.00). Similarly, BRAF V600E+ tumors with lung metastases also demonstrated a preponderance of FDG uptake (WBS: 29%, FDG: 93%, p = 0.02) than BRAF V600E- tumors (WBS: 83%, FDG: 83%, p = 1.00) with lung metastases. Papillary histology featured higher FDG uptake in lung metastasis (WBS: 39%, FDG: 89%, p = 0.03) compared with follicular histology (WBS: 69%, FDG: 77%, p = 1.00). Patients with papillary pattern disease, BRAF V600E+ mutation, or papillary histology had reduced agreement between both modalities in uptake at all metastatic sites compared with those with follicular pattern disease, BRAF V600E- mutation, or follicular histology. Low agreement in lymph node uptake was observed in all patients irrespective of molecular status or histology. Conclusions: The pattern of FDG-PET and radioiodine uptake is dependent on molecular status and metastatic site, with those with papillary histology or BRAF V600E+ mutation featuring increased FDG uptake in distant metastasis. Further study with an expanded cohort may identify which patients may benefit from specific imaging modalities to recognize and surveil metastases.

BIOLOGÍA REPRODUCTIVA Y RELACIONES DE COMPATIBILIDAD POLEN-PISTILO EN UNA COLECCIÓN DE Stevia rebaudiana BERTONI EN ARGENTINA

Stevia rebaudiana Bertoni (Asteraceae) is a diploid species (2n=2x=22) with sexual and asexual reproduction. The sexual propagules are seeds produced by cross-pollination (allogamy) whereas the asexual propagules are either vegetative shoots or apomictic seeds. Various authors have reported that allogamy in this species is promoted by the expression of a sporophytic self-incompatibility (SSI) system. To introduce the cultivation of S. rebaudiana as a production alternative in Tucumán, Argentina, a germplasm collection of this species was established with accessions from four Argentinian provinces in the Famaillá Agropecuarian Experimental Station (EEA Famaillá), National Institute of Agropecuarian Technology (INTA). The reproductive biology of the collection was studied between 2014 and 2021 to develop strategies for breeding and conservation of these genetic resources. Fifty-six genotypes were analyzed, all of them were 2n=2x=22. Pollen viability was high (69.4 to 99.6%) in all the genotypes except in four of them, which exhibited low viability (36.0 to 51.5%) in 2015 and 2017. Forty-eight genotypic combinations were obtained by manual controlled crosses. In 12 of these combinations, one pollen tube was observed in the style zone and, in four of them, one pollen tube was observed in the embryo sac; these observations indicate, respectively, incompatible and compatible pollen-pistil relationships. Normal plump seeds were obtained in all compatible genotypic combinations. The observed incompatibility might be due to the functioning of the sporophytic homomorphic system and/or a cross-incompatibility system. The observed compatibility will allow the planification of controlled crosses within and between accessions of different geographical origins to generate genetically variable progenies for breeding purposes. Key words: genetic resources, incompatibility, internal hybridization barriers, pollen viability

Low-intensity noise exposure takes an essential part in the mechanism of late-onset hereditary hearing loss caused by Abcc1 mutation.

With the development of the social economy, we are exposed to increasing noise in our daily lives. Our previous work found an ABCC1(NM_004996.3:c.A1769G, NP_004987.2:p.N590S) variant which cosegregated with the patients in an autosomal dominant non-syndromic hearing loss family. At present, the specific mechanism of deafness caused by ABCC1 mutation is still not clear. Using the knock-in mouse model simulating human ABCC1 mutation, we found that the occurrence of family-related phenotypes was likely attributed to the combination of the mouse genotype and low-intensity noise. GSH and GSSG are important physiological substrates of ABCC1. The destruction of GSH-GSSG balance in the cochleae of both Abcc1N591S/+ mice and Abcc1N591S/N591S mice during low-intensity noise exposure may result in irreversible damage to the hair cells of the cochleae, consequently leading to hearing loss in mice. The findings offered a potential novel idea for the prevention and management of hereditary hearing loss within this family.

Selection of Superior Potato (Solanum tuberosum L.) by Combined Stability Analysis for Future Breeding Strategies

Abstract Potato is one of the main agricultural commodities and has high economic value. Yield is a trait that becomes a benchmark for user (industry and farmers) in selecting and developing varieties. The selection of superior newly potato somaclones using combined analysis and sustainability index (SI) is still underreported. This study aimed to identify the effect of genotype by environment (growing season) interactions (GEIs), as well as to select superior potato somaclones. The research was conducted in three years (2020 ‒ 2022) in Lembang, West Java, Indonesia. There were 38 somaclones tested in the field, consisting of 37 gamma ray-derived somaclones and one control genotype. The somaclones originated from commercial varieties Agria, Granola, Repita, and Vega. The field trial used a randomized block design that was repeated three times in each year. GEIs were calculated based on a combined ANOVA. Yield stability was assessed using the combined analysis (parametric and non-parametric), genotype plus genotype by environment interaction (GGE) biplot, and sustainability index (SI). Potato somaclones (G), seasons (E) and GEIs were found to have highly significant influence on yield (P &lt; 0.01). According to the combined ANOVA, the GEIs impact accounted for 37.38% of the yield’s total sum of squares. Combining parametric and non-parametric measurements, seven somaclones, P3, P4, P5, P6, P8, P9, and P26, were selected. GGE biplot selected five stable somaclones, namely P3, P4, P22, P23, and P26, while SI selected eight high-yielding and stable somaclones, namely P3, P4, P5, P8, P13, P16, P26, and P32. Based on various stability measurements, three genotypes have been identified as the superior somaclones, namely P3, P4 and P26. This analysis can assist in selecting activities to determine superior somaclones.